Gene Characteristics and Prognostic Values of m(6)A RNA Methylation Regulators in Nonsmall Cell Lung Cancer.
Gene Characteristics and Prognostic Values of m(6)A RNA Methylation Regulators in Nonsmall Cell Lung Cancer.
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DOI：
10.1155/2021/2257066
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发表时间：
2021
影响因子：
--
通讯作者：
Li W
中科院分区：
文献类型：
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作者：
Li N;Chen X;Liu Y;Zhou T;Li W
N6-甲基腺苷 (m6A) 是 mRNA 和长非编码 RNA (lncRNA) 中最常见的内部修饰，与肿瘤发生和癌症进展相关。然而，人们对 m6A 及其调控基因在非小细胞肺癌 (NSCLC) 中的作用知之甚少。在这里，我们系统地探讨了 m6A 相关调控基因在 NSCLC 中的作用和预后意义。 从癌症基因组图谱（TCGA）数据库中下载1057例NSCLC患者的拷贝数变异（CNV）、突变、mRNA表达数据以及相应的临床病理信息。利用分割分析和 GISTIC 算法确定 CNV 的增益和丢失水平。 GSEA旨在探索不同水平的m6A调控基因的相关功能。 Logrank检验用于评估m6A相关基因CNV的预后意义。 在 102 个独立的 NSCLC 样本中鉴定出 10 个 m6A 相关调节因子的基因改变，这些改变与晚期肿瘤分期显着相关。缺失或浅缺失对应于较低的 mRNA 表达，而拷贝数增加或扩增则与 m6A 调控基因的 mRNA 表达增加相关。生存分析显示，FTO 拷贝数丢失的患者无病生存 (DFS) 或总生存 (OS) 较差。此外，YTHDC2 拷贝数丢失也会导致 NSCLC 患者的 OS 较差。此外，FTO 高表达与 mRNA 的氧化磷酸化、翻译和代谢显着相关。 我们的研究结果为更好地理解 m6A 调节因子和 RNA 表观遗传修饰在 NSCLC 发病机制中的作用提供了新的见解。
N6-methyladenosine (m6A) is the most common internal modification present in mRNAs and long noncoding RNAs (lncRNAs), associated with tumorigenesis and cancer progression. However, little is known about the roles of m6A and its regulatory genes in nonsmall cell lung cancer (NSCLC). Here, we systematically explored the roles and prognostic significance of m6A-associated regulatory genes in NSCLC. The copy number variation (CNV), mutation, mRNA expression data, and corresponding clinical pathology information of 1057 NSCLC patients were downloaded from the cancer genome atlas (TCGA) database. The gain and loss levels of CNVs were determined by utilizing segmentation analysis and GISTIC algorithm. The GSEA was conducted to explore the functions related to different levels of m6A regulatory genes. Logrank test was utilized to assess the prognostic significance of m6A-related gene's CNV. The genetic alterations of ten m6A-associated regulators were identified in 102 independent NSCLC samples and significantly related to advanced tumor stage. Deletions or shallow deletions corresponded to lower mRNA expression while copy number gains or amplifications were related to increased mRNA expression of m6A regulatory genes. Survival analysis showed the patients with copy number loss of FTO with worse disease-free survival (DFS) or overall survival (OS). Besides, copy number loss of YTHDC2 was also with poor OS for NSCLC patients. Moreover, high FTO expression was significantly associated with oxidative phosphorylation, translation, and metabolism of mRNA. Our findings provide novel insight for better understanding of the roles of m6A regulators and RNA epigenetic modification in the pathogenesis of NSCLC.